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Diagnosis and Classification

Mitochondria contain their own genetic information in the form of a circular DNA molecule of l6 569 base pairs that encodes l3 subunits of the oxidative phosphorylation complex, 2 ribosomal RNAs and 22 transfer RNAs (tRNA) needed for mitochondrial protein synthesis. Several mitochondrial cytopathies and syndromes caused by point mutations, deletions or duplications of mitochondrial DNA (mtDNA) and characterized by decreased oxidative phosphorylation are associated with diabetes (64,65)....

Table 3.3 summarizes the etiological classification of diabetes mellitus. Etiological and clinical stages are presented in Figure 3.2. The concepts for new staging etiological classification were proposed by Kuzuya and Matsuda (20). Their proposals sought to separate clearly the criteria related to etiology and those related to degree of deficiency of insulin or insulin action and to define each patient on the basis of these two criteria. The newly suggested WHO classification and the new ADA...

The ADA classification and the proposed WHO classification encompass both clinical stages, etiological types of diabetes mellitus and other categories of hyperglycemia (Table 3.3). Diabetes may progress through several clinical stages during its natural history regardless of its etiology. The clinical staging reflects this specific aspect. Moreover, individual subjects may move from stage to stage in either direction (Figure 3.2). Even in the DIABETES MELLITUS DIAGNOSIS AND CLASSIFICATION Table...

Many factors suggest that environmental factors are important determinants of Type 1 diabetes. It has already been noted that environmental factors are implicated by the discordance rate in monozygotic twins and the higher prevalence of autoimmunity in non-diabetic twins than in other first-degree relatives. Other indicators that environmental factors are involved include the seasonal variation in disease onset (15) and the rising incidence of Type 1 diabetes in Europe and many other parts of...

Type 2 diabetes in African Americans is a heterogeneous disorder with insulin-sensitive and insulin-resistant variants identified using the eu-glycemic insulin clamp method (77). In contrast, most studies (66,78,79) with few exceptions (80,81,82) report Type 2 diabetes to be a disorder of insulin resistance. The two variants are notably different in terms of cardiovascular risk factors and body composition (72,83,84). The insulinsensitive variant has low lipid levels while the insulin-resistant...

MODY is a familial form of non-insulin-dependent diabetes with autosomal dominant inheritance. Hyperglycemia in MODY subjects usually develops at childhood, adolescence or young adulthood, and is associated with primary insulin-secretion defects The Epidemiology of Diabetes Mellitus. An International Perspective. Edited by Jean-Marie Ekoe, Paul Zimmet and Rhys Williams. 2001 John Wiley amp Sons Ltd. 3,12 . The well-defined mode of inheritance with high penetrance and the early age of onset of...

At the time of diagnosis, there is at least a small number of functioning beta-cells in most patients, irrespective of the type and etiology of diabetes. Regulation of insulin release, as well as insulin signaling, are disturbed in response to prolonged hyperglycemia this glucose toxicity is resolved by treatment of the newly-diagnosed disease, endogenous insulin secretion and insulin activity resume for at least a short interval in most patients 59 . The 'honeymoon' seen in the first few...

In different populations, the distribution of blood glucose may vary greatly. In one of the early studies of diabetes epidemiology performed in the USA and based on medical history, urine glucose tolerance in a defined community, Wilkerson and Krall reported a large variation in the distribution of blood glucose values within the eight screenee age groups 17 . One pertinent fact was observed higher levels of blood glucose were apparent with aging. In the 75-79 years age group, 50 of subjects...

Other studies have also shown that dietary factors could precipitate the expression of diabetes. In Iceland the traditional high intake of smoked and cured mutton during Christmas and New Year was correlated with an excess of boys under the age of 15 years born in October who developed Type 1 diabetes 142 N-nitroso compounds were found in the smoked and cured mutton, and it was postulated that nitrosamines which are known to cause cancer are also capable of damaging the pancreatic -cells before...

Glucokinase phosphorylates glucose to glucose-6-phosphate in pancreatic beta-cells and hepato-cytes, and plays a major role in the regulation and integration of glucose metabolism 30 . More than 80 different GCK mutations associated with MODY have been observed to date 15,31 . Expression studies have shown that the enzymatic activity of the mutant proteins was impaired 32 , resulting in decreased glycolytic flux in pancreatic beta-cells 33 . This defect translates in vivo as a glucose-sensing...

Taken together, all the genetic defects described so far account for not more than a few percent of all cases of Type 2 diabetes. The majority of the susceptibility genes to Type 2 diabetes still remains to be described. The fact that Type 2 diabetes is a genetically heterogeneous disorder implies that several primary defects contribute to the susceptibility to the disease. It seems reasonable to postulate that the combinations of deleterious genes are not the same in the obese or the lean...

The epidemiological attempt to study the natural history and pathogenesis of diabetes as a whole can only rely on one common and stable factor, high blood glucose, despite the wide variation in clinical manifestations and various contributing factors. However, high blood glucose alone does not answer all the questions. Over the past 30 years, evidence has accumulated that numerous and etiologically different mechanisms genetic, environmental or immunologic processes may play an important role...

National Public Health Institute, Helsinki, Finland Type 1 diabetes mellitus is one of the major non-communicable diseases in children aged 14 years or under 1 . Although the etiology of Type 1 diabetes is still unknown, it is currently assumed that both genetic 2-5 and environmental factors 6-17 operate together in a process in the pancreatic beta-cells, leading to the onset of diabetes. The role of HLA genetics in the etiology of Type 1 diabetes is well understood, but neither the mode of...

These causes of diabetes are unusual and result from genetically determined abnormalities of insulin action. The metabolic abnormalities associated with mutations of the insulin receptor may range from hyperinsulinemia and modest hyper-glycemia to severe symptomatic diabetes 60,61 . Acanthosis nigricans may be present in some of these individuals. Women may have virilization and have enlarged cystic ovaries. This syndrome was termed Type A insulin resistance in the past 60 . Two pediatric...

The suggestion that refined carbohydrates, and sugars in particular, might be involved in the aetiology of Type 2 diabetes dates back to the writings of early Indian physicians. However, in the 1960s, Yudkin resurrected the suggestion that high intakes of sucrose may be particularly important in the aetiology of Type 2 diabetes when he drew attention to the positive correlation between intakes of sucrose and diabetes prevalence in 22 countries 11 . But it has subsequently become clear that the...

Polycystic ovary syndrome is typically diagnosed in patients with symptoms of androgen excess, i.e. infertility, hirsuitism or oligomenorrhea, and elevated serum androgen levels, and is associated with insulin resistance. The prevalence of polycystic ovary syndrome is 20 of asymptomatic women in England as detected by ultrasound 97,98 Among 18-40-year-old Asian Indian women in England the prevalence on ultrasound was gt 50 , and polycystic ovary syndrome was significantly associated with...

Insulin-treated patients who do not have access to facilities for self-measurement of blood glucose should test urine samples passed after rising, before main meals, and before going to bed. Patients with Type 2 diabetes do not need to monitor their urine so frequently. Urine tests are of somewhat limited value, however, because of the great variation in urine glucose concentration for given levels of blood glucose. The correlation between blood and urine glucose may be improved a little by...

During the 1970s published reports suggested wide geographical differences in incidence of Type 1 diabetes 18-24 , but the lack of standardized data made it difficult to determine the true magnitude of the worldwide variation in Type 1 diabetes morbidity. Standardized collection and analysis of epidemiological data of Type 1 diabetes started in the 1980s and since the mid-1980s Type 1 diabetes registries have been established in many parts of the world. The Diabetes Epidemiology Research...

During childhood the incidence of Type 1 diabetes increases with age, and in both sexes the peak in incidence is seen in puberty. This peak seems to occur somewhat earlier in females than in males. Most of the individual studies have been based on a relatively small number of cases and therefore the overall picture with regard to a possible sex-associated effect has remained unclear. Nevertheless, only 20-50 of all patients with Type 1 diabetes are diagnosed during childhood, although most of...

The oral glucose tolerance test OGTT is principally used for diagnosis when blood glucose levels are equivocal, during pregnancy, or in an epidemiological setting to screen for diabetes and impaired glucose tolerance. The OGTT should be administered in the morning after at least 3 days of unrestricted diet greater than 150 g of carbohydrate daily and usual physical activity. The test should be preceded by an overnight fast of 8-14 h, during which water may be drunk. Smoking is not permitted...

Compared with Type 1 diabetes, MODY exhibits a milder course. Onset is often asymptomatic, and DKA usually does not develop even in the presence of chronic hyperglycemia. The majority of studies on MODY have focused on European-origin patients, and almost all of the specific genetic associations which have been reported are restricted to whites. The term MODY, then, may be most properly used only with reference to European-origin patients. A case definition for MODY offered by Tattersall and...

Cardiorespiratory fitness defined by measurement of oxygen consumption at a submaximal or maximal workload on a graded treadmill or bicycle ergometry, has been used extensively to validate physical activity assessment tools 31-33 . The rationale for using fitness as a validation method for physical activity extends from the consistent findings that aerobic activity improves cardiorespiratory fitness 34 . When well-defined laboratory criteria are used, physical fitness testing can be highly...

To determine if gestational diabetes is present in pregnant women, a standard OGTT should be performed after overnight fasting 8-14 h by giving 75 g anhydrous glucose in 250-300 ml water Annex 1 . Plasma glucose is measured fasting and after 2 h. Pregnant women who meet WHO criteria for diabetes mellitus or IGT are classified as having Gestational Diabetes Mellitus GDM . After the pregnancy ends, the woman should be reclassified as having either diabetes, or IGT, or normal glucose tolerance...

Recent epidemiological studies have related physical activity to improved glucose tolerance, insulin sensitivity and reduced prevalence and incidence of diabetes in various ethnic groups see 1,2 for a review of the literature . Physical activity is also thought to protect against a wide range of other diseases and adverse outcomes, including cardiovascular disease, stroke, colon cancer, functional decline, and all-cause mortality 3-11 . Additionally, physical inactivity has been related to...

A number of clinic-based studies in the US demonstrate an increasing rate of diagnosis of Type 2 diabetes among children. At the Cincinnati Children's Hospital, the major pediatric referral hospital in the region, 54 of 1027 diabetic patients age 0-19 5.3 met criteria for Type 2 diabetes over a 13-year period. Type 2 diabetes accounted for 2-4 of all diabetes diagnosed before 1992 in 1992-94 the proportion increased to 8-17 of all incident cases. Most patients were diagnosed during a routine...

Although the susceptibility to Type 1 diabetes is inherited, the main problem in prevention of Type 1 diabetes using the high-risk approach is that only 12-15 of Type 1 diabetes occurs in families with first degree relatives with Type 1 diabetes. The majority of Type 1 diabetes about 85 occurs in a sporadic fashion and is therefore unaccounted for in most studies aimed at estimating risk and predictive value of certain markers. One has to bear in mind not only that about one-third of the...

Impaired glucose tolerance IGT was considered a class in the previous WHO classification but is now categorized as a stage in the natural history of disordered carbohydrate metabolism. A stage called 'impaired fasting hyperglycemia' or impaired fasting glycemia IFG or 'non-diabetic fasting hyperglycemia' is now recognized as these people also appear to be at greater risk for progression to diabetes and macrovascular disease, although prospective data are sparse and early data suggest a lower...

The male female excess in the incidence of Type 1 diabetes is shown in Table 7A.4 and Figures 7A.2 and 7A.3. Depending on the sex- specific incidence the sex ratio was calculated in the following way A. The incidence is higher in males than in females IM IF 1 B. The incidence is higher in females than in males IF IM 1 To distinguish the female excess from the male excess in incidence, the rate ratio is expressed as negative in case of female excess in incidence. The female excess in the...

Increased plasma insulin levels were associated with higher triglyceride, glucose and LDL-cholesterol levels in both African American and white non-diabetic subjects this association was strongest for lean and less so for obese subjects 51,76 . Among young African American subjects, after adjusting for percent body fat, WHR was associated with various cardiovascular risk factors triglyceride, HDL-cholesterol, LDL cholesterol women only , apo-lipoprotein A-1 and B, uric acid, systolic BP fasting...

These have been used to assess physical activity and, more often, to help validate subjective measures of activity. Examples of these tools include pedometers, activity movement monitors and accelerometers. Pedometers, worn in the shoe or on the hip, estimate movement by responding to vertical movement of the body. Recent enhancements include the ability to adjust for stride length and body weight, for a prediction of kilocalories expended 25 . The Large Scale Integrated LSI activity monitor...

The appearance of persistent ketonuria associated with hyperglycemia or high levels of glycosuria in the diabetic patient points to an unacceptably severe level of metabolic disturbance and indicates an urgent need for corrective action. The patient should be advised to test for ketone bodies acetone and aceto-acetic acid when tests for glucose are repeatedly positive, or when there is substantial disturbance of health, particularly with infections. Rothera's sodium nitroprusside test may be...